(1) FIELD OF THE INVENTION
This invention relates to asialoganglioside related compounds, and emore particularly to methods for producing asialo G.sub.M1, asialo G.sub.M2 and intermediate compounds for use in producing the same.
(2) DESCRIPTION OF THE PRIOR ART
Glycolipids found in mammal cells are glycosides between ceramides, which are sphingosines (long chain amino alcohols) to which aliphatic acids have been attached through an amide linkage, and one or more sugars such as glucose, galactose, N-acetyl glucosamine, N-acetyl galactosamine, fucose, sialic acid, etc. Among these glycosides, those containing sialic acid are called gangliosides.
Compounds obtained by removing sialic acid residue from gangliosides are called asialoganglioside, which are naturally found in a smaller amount than gangliosides, and therefore which have been prepared by hydrolysis of corresponding gangliosides with formic acid or sialidase.
Asialo-G.sub.M1 -ganglioside or gangliotetraosylceramide 1 was reported to be present as a rat erythrocyte antigen and as a mouse natural killer cell marker (1). Antibodies directed to asialo-G.sub.M1 -ganglioside have been used to detect acute lymphatic leukemia cells (1). The structure of 1 was determined by partial degradation and methylation analysis (2-4). Asialo-G.sub.M2 -ganglioside or gangliotriosylceramide 24 has been isolated from the brain of a Tay-Sachs patient (1), guinea pig erthrocytes (5), mouse Kirsten tumor (6), and rat hepatoma (7).
Due to their functions as tumor-associated markers, three independent approaches to the synthesis of the glycan part of asialo-G.sub.M1 - and asialo-G.sub.M2 -ganglioside have recently been reported (8-10).
1. Hakomori S. (1983) in Handbook of Lipid Research, Vol 3, Sphingolipid Biochemistry, eds. Kanfer J. N., Hakomori S., Plenum Press, New York, p 121-29. PA0 2. Svennerholm L. (1962) Biochem Biophys Res Commun. 9:436-41. PA0 3. Kuhn R., Wiegandt H. (1963) Chem. Ber. 96:866-80. PA0 4. Kuhn R., Egge H. (1963) Chem. Ber. 96:3338-48. PA0 5. Seyama Y., Yamakawa T. (1974) J. Biochem. (Tokyo) 75:837-42. PA0 6. Rosenfelder G., Young W. W. Jr. Hakomori S. (1977) Cancer Res. 37:1333-39. PA0 7. Hirabayashi Y., Taki T., Matsumoto M., Kojima K. (1978) Biochim. Biophys. Acta 529:96-105. PA0 8. Wessel H-P., Iversen T., Bundle D. R. (1984) Carbohydr. Res. 130:5-21. PA0 9. Sabesan S., Lemieux R. U. (1984) Can. J. Chem. 62:644-54. PA0 10. Paulsen H., Paal M., Hadamczyk D., Steiger K-M. (1984) Carbohydr. Res. 131:C1-C5.
As mentioned above, asialogangliosides exist mainly in the outer surfaces of bilayer of mammal cell membranes. Recent studies show that gangliosides play important roles in reception and recognition of, and response to, information in cells, receptor mechanism, differentiation, cell propagation, malignant cell transformation, cell behavior, etc.
However it is very difficult to isolate asialogangliosides from an organism in which they exist in a smaller amount. Therefore precise synthesis of such asialogangliosides is necessary for the elucidation of the precise correlation between biological information and the molecular structure of the oligosaccharides.